What happens when your polygenic risk score says one thing and your body says another? Broad Institute geneticist Dr. Nikolas Baya studies the people who don't match their genetic prediction, and the rare variants that often explain the gap.

Dr. Jeremy Koenig talks with Dr. Nikolas Baya, a postdoctoral researcher at Massachusetts General Hospital and the Broad Institute, about his recently published UK Biobank study showing that people who deviate from their polygenic score are enriched for rare variants in genes linked to rare disease. Nik explains why that makes polygenic scores useful as a filter for rare disease diagnosis, how protective variants in genes like PCSK9 have led to new drug targets, and why an estimated 240 million people worldwide live with a rare genetic disease. He also walks through the BRaVa browser, a free tool for the Biobank Rare Variant Analysis consortium that pools rare variant results across ancestrally diverse biobanks, which he built with Claude Code in about two weeks. And he explains why he still writes by hand, comparing heavy AI use to eating cake: you feel full and productive, but it isn't intellectually nourishing.

Dr. Nikolas Baya is a postdoctoral researcher at Massachusetts General Hospital and the Broad Institute of MIT and Harvard, with a DPhil from the University of Oxford's Genomic Medicine and Statistics program.

Connect with Nik: https://www.linkedin.com/in/nikolas-baya/

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